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通过多尺度分析解决瘤微环境异质性,预测三阴性乳腺癌的免疫治疗反应

Shihao Sun¹, Shuang Chen², Kaiyuan Li³

¹Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Frontiers in oncology

|September 4, 2025

概括

在三阴性乳腺癌 (TNBC) 中,BRCA1状态会影响瘤微环境. 这项研究确定ISG15是预测TNBC患者免疫治疗反应的潜在生物标志物.

科学领域:

在三阴性乳腺癌 (TNBC) 中研究瘤微环境.
使用多种经济学数据集成进行综合分析.
探索BRCA1突变在免疫治疗反应中的作用.

背景情况:

三重阴性乳腺癌 (TNBC) 免疫治疗结果仍然不理想.
BRCA1突变与免疫治疗反应有关,但临床结果有限.
了解TNBC异质性对于提高治疗疗效至关重要.

研究的目的:

阐明BRCA1状态对TNBC瘤微环境的影响.
确定与免疫治疗反应相关的新生物标志物和细胞表型.
在TNBC中开发免疫治疗反应的预测模型.

主要方法:

空间,单细胞和大量RNA测序数据的整合.
多尺度分析以确定癌症相关纤维细胞 (CAF) 表型和生物标志物.
高分辨率,无标签的蛋白质组学用于蛋白质水平的验证.
构建免疫检查点抑制剂 (ICI) 反应预测系统的机器学习管道.

主要成果:

与BRCA1突变体相比,野生型TNBC表现出T细胞耗尽和树突细胞耐受性的增加.
使用伪时间分析识别MEG3+前CAF子组.
ISG15成为一种潜在的免疫调节生物标志物.
一个预测模型在预测免疫治疗反应方面显示出希望.

结论:

TNBC表现出显著的细胞异质性.
ISG15是预测TNBC免疫治疗反应的候选生物标志物.
基于ISG15的预测系统为预测ICI响应提供了一个潜在的框架.

关键词:

发生BRCA1突变与癌症相关的纤维细胞免疫检查点抑制剂三重阴性乳腺癌瘤微环境

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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...